Cytokines and psoriasis

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Psoriasis is an immune dysfunction disease associated with abnormal level of cytokine .It’s associated with (elevated level TNFα, IFN- γ, IL-la , IL-13, TGF-β1 , IL-6, _[53] , IL-2, IL – 7, IL - 18IL – 4, IL - 10 vascular endothelial growth factor ( VEGF )and other cytokines in lesional skin ).

It has been suggested that the expression of IL-12 might play an important role in certain inflammatory skin diseases. Psoriasis vulgaris is a chronic inflammatory type cytokine-related cutaneous disease, which is characterized by infiltrates of activated memory T cells that have a high IFN- γ expression. An enhanced expression of IL-12 mRNA and protein was found in psoriatic lesional skin compared with nonlesional and normal skin, and a causative relationship to the high IFN- γ expression in lesional skin was suggested. IL-23 was found during a genome scan for the IL-6/IL-12 cytokine family.

 IL-23 is a heterodimer, sharing a p40 subunit with IL-12 but having a distinct p19 subunit.IL -23 binds to IL-12Rβ1 but not IL-12Rβ2. The receptor for this cytokine is heterodimeric and uses a novel second subunit, IL-23R, which is a member of the hematopoietin receptor family. IL-23 plays a role in type 1-polarized T cell immune responses. IL 23 is produced by activated dendritic cells ,macrophages and keratinocytes. IL-23 amplifies and stabilizes a new CD4(+)T-cell subset, Th17 producing IL-17.

In other study state that that cutaneous resident DCs, LCs, and dermal DCs are capable of inducing distinct IL-22- producing CD4+ T cells, possibly Th22, from both whole peripheral T cells and naive T cells. Until very recently, IL-22 had been considered a Th17-associated cytokine. Indeed, in previous studies, although Th1 cells produced more IL-22 in comparison to Th2 cells or unpolarized T cells, Th17 cells were clearly the dominant IL-22 producers at both mRNA and protein levels . These data established that IL-22 was an effector cytokine of Th17 cells. Indeed, psoriasis skin lesions contain a population of T cells that cosynthesize IL-17 and IL-22, but the majority of IL-22-producing T cells are neither Th17, Th1, nor Th2 .

 In AD, there is an even larger population of T cells that uniquely synthesize IL-22 . Moreover, two independent groups have recently identified a human helper T cell population producing abundant IL-22 that is distinct from Th17 and Th1 . In their paper, Trifari et al. named this unique population Th22 . The unique characteristic of DCs is their ability to polarize naive helper T cells into Th1, Th2, and Th17 cells. DCs reside in antigen-capture areas related to epithelial surface and secondary lymphoid organs . Indeed, using activated conventional DCs and plasmacytoid DCs, Trifari et al. have also demonstrated that human

DCs actually induce the development of Th22 cells from naive T cells . According to their results, plasmacytoid DCs are more powerful than conventional DCs in the expansion of Th22 cells. However, it was unknown whether tissue resident DCs, including cutaneous DCs, were actually able to induce this unique IL-22-producing helper T cell population. Thus, in this study is unique evidence illustrating that tissue resident DCs can induce the differentiation of Th22 cells. State that LCs and dermal DCs are able to induce IL-22-producing T cells lacking IL-17 production at least conditionally. Stimulation of keratinocytes with IL-22 leads to the induction of antimicrobial peptides, such as S100A7 and β-defensin . In addition, this cytokine has much stronger effects in regulating hyperplasia and differentiation in keratinocytes . In vitro, IL 22 induces marked acanthosis and hypogranulosis and suppression of terminal differentiation of cultured reconstructed epidermisIt has also been reported that polarization of Th22 cells is largely, but not completely, dependent on IL-6 and TNF-α

TGF-_β1 levels increased in plasma and scales of psoriatic patient , TGF-_β1 can induces T-cell migration , chemoattractant for neutrophils and monocytes / macrophages in early stages of infection and induces monocytes to express CD16 , thereby predisposing these cells to become migratory CD86⁺ DC_S. In skin ,thes proinflammatory  processes can overcome antiprloferative effects that TGF-_β1 exerts directly on keratinocytes and can lead to the development of psoriasis- like disease in mice.

Although the simultaneous presence of IL-17 and IL-22 has been proposed to be the “signature” of Th17 cells, PGE2 enhances IL-17 and decreases IL-22 production and are reminiscent of a similar dissociation observed in mouse Th17 cells generated in the continuous presence of TGF-β and IL-6 opposed to priming in the presence of TGF-β and IL-6 followed by expansion in IL-23. IL-22 is considered a proinflammatory cytokine with a distinct role in the generation of psoriatic skin lesions.

In other study it reported that serum levels of proinflammatory cytokines (TNF- α, IL-2R and IL - 6 ) in psoriasis vulgaris In patients which are of major clinical relevance to the clinician and their correlation with severity of psoriasis. some particular stress-induced effects on circulating lymphocytes with implications for the cutaneous inflammation in this chronic relapsing skin disease .